1452-94-4Relevant academic research and scientific papers
2-Azaallyl anions: key models for the elaboration of alkyl-, amino- and hydroxy-1,7-naphthyridine derivatives
Couture, Axel,Grandclaudon, Pierre,Simion, Cristian,Woisel, Patrice
, p. 2643 - 2646 (1995)
A variety of 5-alkyl-, 5-amino- and 5-hydroxy-6,8-diaryl-1,7-naphthyridines have been efficiently prepared by the treatment of suitable 2-azaallyl anions with diversely functionalized 2-halogenopyridines.
Design, synthesis and molecular docking studies of new azomethine derivatives as promising anti-inflammatory agents
Desai, Sulaksha R.,Desai, Vidya G.,Pissurlenkar, Raghuvir R.
supporting information, (2022/01/24)
Herein, we synthesized a series of Ibuprofen-based 4a-k, quinoxaline-based 9a-f and pyridine-based 13a-h azomethine derivatives and studied their anti-inflammatory potency. The in-silico docking studies of the synthesized compounds 4a-k revealed better af
2-(1H-pyrazol-3-yl) pyridine derivative as well as preparation method and application thereof
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Paragraph 0071-0074, (2021/06/22)
The invention belongs to the field of medicinal chemistry, particularly relates to a compound shown in a formula I, or a stereoisomer, salt, prodrug or solvate thereof, and also relates to a preparation method of the compound and application of the compound in preparation of drugs for treating related diseases mediated by histone demethylase JMJD6.
Discovery of a new class of JMJD6 inhibitors and structure–activity relationship study
Wang, Tianqi,Zhang, Rong,Liu, Yang,Fang, Zhen,Zhang, Hailin,Fan, Yan,Yang, Shengyong,Xiang, Rong
supporting information, (2021/05/27)
JmjC domain-containing protein 6 (JMJD6) has been thought as a potential target for various diseases particularly cancer. However, few selective JMJD6 inhibitors have been reported. In this investigation, molecular docking and biological activity evaluation were performed to retrieve new JMJD6 inhibitors, which led to the identification of a hit compound, J2. Further structural optimization and structure–activity relationship (SAR) analysis towards J2 were carried out, which gave a new potent JMJD6 inhibitor, 7p. This compound showed an IC50 value of 0.681 μM against JMJD6, but displayed no activity against other tested JmjC domain-containing protein family members, indicating good selectivity (>100 fold). Collectively, this investigation offers a selective JMJD6 inhibitor, which could be taken as a lead compound for subsequent drug discovery targeting JMJD6.
Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes
Asquith, Christopher R. M.,Awad, Dominik,Catta-Preta, Carolina M. C.,Cou?ago, Rafael M.,Drewry, David H.,Eduful, Benjamin J.,Frigo, Daniel E.,Hossain, Mohammad Anwar,Langendorf, Christopher G.,Liang, Yi,Lin, Chenchu,Nay, Kévin,O'Byrne, Sean N.,Oakhill, Jonathan S.,Picado, Alfredo,Pilotte, Joseph R.,Pulliam, Thomas L.,Santiago, André De S.,Scott, John W.,Temme, Louisa,Wells, Carrow I.,Willson, Timothy M.,Zonzini Ramos, Priscila,Zuercher, William J.
, p. 10849 - 10877 (2021/08/03)
CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chemical probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934, a total of 32 compounds, composed of single-ring, 5,6-, and 6,6-fused heteroaromatic cores, were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. Compared to GSK650394 and STO-609, 13 compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs.
Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents
Sultana, Faria,Saifi, Mohd Aslam,Syed, Riyaz,Mani, Geeta Sai,Shaik, Siddiq Pasha,Osas, Egharevba God'Shelp,Godugu, Chandraiah,Shahjahan, Syeda,Kamal, Ahmed
, p. 7150 - 7161 (2019/05/17)
A series of 2-anilinopyridyl linked benzothiazole-hydrazone conjugates (5a-aa) were designed, synthesized and evaluated for their in vitro cytotoxic potency against a panel of cancer cell lines like mouse skin melanoma (B16F10), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), triple negative breast cancer (MDA-MB-231) and normal lung epithelial (L132) cell lines. Preliminary screening results revealed that some of these conjugates like 5i and 5l exhibited a significant antiproliferative effect against human breast cancer (MCF-7) with IC50 values of 1.03 and 1.69 μM respectively. Further, detailed biological studies of this promising conjugate (5i) were carried out on MCF-7 cells. The flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase in a dose dependent manner. Furthermore, in order to determine the effect of the conjugate on cell viability, various cell based assays such as clonogenic assay, ethidium bromide staining, Hoechst staining, detection of ROS generation and annexin V-FITC/PI assays were performed. In these studies, apoptotic features were clearly observed indicating that this conjugate inhibited cell proliferation by apoptosis.
A microwave synthesis 2 - halogenated nicotinate and intermediates thereof
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, (2018/05/16)
The invention discloses a method for synthesizing 2-halogenated nicotinic acid ester and intermediates thereof through microwave method. The method comprises the following steps: adding substitute amino acrolein, a catalyst and cyan-acetic ester into a reactor, carrying out reaction under microwave radiation, and tracking the reaction till substitute amino acrolein disappears to prepare and obtain reaction liquid of the intermediates of 2-halogenated nicotinic acid ester; adding hydrogen halide into the reaction liquid, continuously carrying out reaction, and tracking and monitoring the reaction till the reaction is complete; adding alkali liquor into the reaction liquid to adjust the pH value to 5-6; carrying out standing delamination to obtain an aqueous layer and an organic layer; extracting the aqueous layer with an organic solvent, combining the extracted aqueous layer with the organic layer, and carrying out refinement to prepare and obtain 2-halogenated nicotinic acid ester. The synthesis method of 2-halogenated nicotinic acid ester related to the invention has the advantages of beingenvironment-friendly, short in reaction time, simple to operate, high in product yield and good in quality.
A ultrasonic process for synthesizing 2 - halogenated nicotinate and intermediates thereof
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Paragraph 0042; 0043, (2018/04/21)
The invention discloses a method for synthesizing 2-halogenated ester nicotinate and a 2-halogenated ester nicotinate intermediate according to an ultrasonic method. The method comprises the following steps: adding substituent amino acrolein, a catalyst and cyanacetic ester into a reactor for a reaction under ultrasonic radiation; tracing the reaction till substituent amino acrolein is disappeared, thereby obtaining a reaction solution I containing the 2-halogenated ester nicotinate intermediate; then, adding halogen hydride into the reaction solution I for another reaction to obtain a reaction solution II; tracing and monitoring the reaction till completion; adding a lye into the reaction solution II to adjust the pH value of the reaction solution II to be 5-6; carrying out standing stratification to obtain a water layer and an organic layer; conducting extraction on the water layer by utilizing an organic solvent, and then combining the extraction solution with the organic layer; carrying out refining to obtain 2-halogenated ester nicotinate. Through the adoption of the method, an organic synthesis reaction can be effectively facilitated, the reaction speed and yield can be improved, and the environmental protection can be promoted; the reaction time is short and the operation is simple, that is, the organic synthesis reaction can be finished within 2 hours in general; the product yield and quality are high; specifically, the product yield can reach 90% or higher, and exceed that achieved according to the conventional solvent heating reflux method.
Method using hydrothermal method to synthesize 2-halogeneated nicotinate and 2-halogeneated nicotinic acid
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Paragraph 0041; 0042, (2017/11/01)
The invention discloses a method using a hydrothermal method to synthesize 2-halogeneated nicotinate and 2-halogeneated nicotinic acid and relates to the field of chemical synthesizing. The method uses substituted amino acrolein, catalyst, catalyst assistant, water and cyanoacetate as raw materials to synthesize the 2-halogeneated nicotinate and the 2-halogeneated nicotinic acid through the hydrothermal method. Compared with the prior art, the method is environmentally friendly, easy in separation, high in product yield, good in product quality, capable of achieving large-scale industrial production favorably, and the like.
Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors
Bayliss, Tracy,Robinson, David A.,Smith, Victoria C.,Brand, Stephen,McElroy, Stuart P.,Torrie, Leah S.,Mpamhanga, Chido,Norval, Suzanne,Stojanovski, Laste,Brenk, Ruth,Frearson, Julie A.,Read, Kevin D.,Gilbert, Ian H.,Wyatt, Paul G.
, p. 9790 - 9806 (2017/12/26)
N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.
